Planned administration of blood transfusions to recipients, prior to organ transplantation, is an accepted procedure to improve allograft survival. While the beneficial effect of transfusion is accepted, the precise mechanisms by which transfusion improves graft survival are not fully understood. One of the proposed mechanisms of action is the induction of suppressor cells. Suppressor cells have been demonstrated in transfused cardiac-grafted mouse recipients. Using the mouse heart transplant model, the overall objectives of this proposal are to assess the role of MHC and non-MHC alloantigens on suppressor cell induction, characterize such cells, and begin to determine the possible target(s) of suppressor cell action. Specific aims are to 1) define the specificity of the cells, 2) establish how long after transfusion they are detectable, 3) determine the splenic cell subset(s) which mediates this effect and 4) compare the suppression generated from non-H-2 histocompatibility antigens to suppression induced by H-2 alloantigens. The mode of suppressor cell action on target cells also remains to be eluciated. It has been suggested that suppressor cells act at the interleukin 2 (lymphokine secreted by helper T cells) level of cellular activation. We plan to test the hypothesis that transfusion-induced suppressors inhibit IL-2 activity. A greater understanding of this phenonmenon would lead to development of the best strategies for the management of blood transfusions in patients, with minimal recipient sensitization to donor antigens.